Hypothesis: do voltage-gated H(+) channels in alveolar epithelial cells contribute to CO(2) elimination by the lung?

Although alveolar epithelial cells were the first mammalian cells in which voltage-gated H(+) currents were recorded, no specific function has yet been proposed. Here we consider whether H(+) channels contribute to one of the main functions of the lung: CO(2) elimination. This idea builds on several observations: 1) some cell membranes have low CO(2) permeability, 2) carbonic anhydrase is present in alveolar epithelium and contributes to CO(2) extrusion by facilitating diffusion, 3) the transepithelial potential difference favors selective activation of H(+) channels in apical membranes, and 4) the properties of H(+) channels are ideally suited to the proposed role. H(+) channels open only when the electrochemical gradient for H(+) is outward, imparting directionality to the diffusion process. Unlike previous facilitated diffusion models, HCO(-)(3) and H(+) recombine to form CO(2) in the alveolar subphase. Rough quantitative considerations indicate that the proposed mechanism is plausible and indicate a significant capacity for CO(2) elimination by the lung by this route. Fully activated alveolar H(+) channels extrude acid equivalents at three times the resting rate of CO(2) production.